The Leicester flanker has undergone surgery after suffering the injury during Tigers’ Aviva Premiership victory over Worcester three days ago.
Leicester rugby director Richard Cockerill said that 27-year-old Croft, who has won 38 England caps and toured twice with the British and Irish Lions, will not play again this term.
Croft took a bang to his knee during the closing minutes of Sunday’s game.
Cockerill said further investigation revealed a ruptured anterior cruciate ligament and Croft subsequently underwent reconstuctive surgery.
“It’s horrendous bad luck for Tom because it is only last year that he came back from a very bad neck injury and did so well for England, but the Lions as well,” Cockerill added. “But these things happen. Tom will make a full recovery, but it’s his season over.
“It is a blow, but we have just got to get on with things.”
Croft suffered a career-threatening neck injury in April last year, but he returned to action eight months later and forced himself back into England contention, starting the final game of last season’s RBS 6 Nations Championship against Wales.
His form was then sufficient to warrant a place on the Lions tour, where he started the first Test and went on as a replacement during the second.
Croft’s absence will be a huge blow to England head coach Stuart Lancaster, who would have viewed him as an integral part of his plans, both for the November internationals and the Six Nations. In addition to his neck problem, Croft has twice previously fought back from knee injuries during a career of extreme highs and lows.